 |
PDBsum entry 6est
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Hydrolase(serine proteinase)
|
PDB id
|
|
|
|
6est
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Interaction of the peptide cf3-Leu-Ala-Nh-C6h4-Cf3 (tfla) with porcine pancreatic elastase. X-Ray studies at 1.8 a.
|
|
|
Authors
|
|
I.Li de la sierra,
E.Papamichael,
C.Sakarellos,
J.L.Dimicoli,
T.Prangé.
|
|
|
Ref.
|
|
J Mol Recognit, 1990,
3,
36-44.
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
The peptide trifluoroacetyl-Leu-Ala-(p-trifluoromethylanilide), is a reversible
inhibitor of pancreatic porcine elastase and is characterized by a Km of 2.5 x
10(-8) M. Co-crystals of the 1:1 complex were obtained in an acetate buffer +
dimethylformamide solution at pH 5.7. Diffraction data were recorded on films at
the LURE synchrotron facility. The inhibitor was localized on difference Fourier
maps, and the refinement of the structure was performed by simulated annealing
(XPLOR). The current agreement factor is R = 19% (for 13224 observed structure
factors and 1.8 A effective resolution). The RMS deviations from ideality of
bond distances and angles are 0.02 A and 2 degrees, respectively. The inhibitor
molecule was found in the active site, bent around the side chain of Phe-215 in
a geometry that resembles the previously reported structure of the CF3-Lys-Ala
complex at 2.5 A, in a parallel beta-sheet association with the loop 214-216.
The analysis of the close contacts (less than 3.5 A) indicates that the
trifluoromethylamide bond interacts with the active site and not the Leu-Ala or
Ala-anilide bonds. The two fluorinated groups of the inhibitor exhibit different
specificities: the trifluoroacetyl group (N terminus) is tightly stacked between
the two chain loops 191-195 and 213-215, while the trifluoromethylanilide (C
terminus) shows less specificity and only a single contact.
|
|
|
Secondary reference #1
|
|
|
Title
|
|
The atomic structure of crystalline porcine pancreatic elastase at 2.5 a resolution: comparisons with the structure of alpha-Chymotrypsin.
|
|
|
Authors
|
|
L.Sawyer,
D.M.Shotton,
J.W.Campbell,
P.L.Wendell,
H.Muirhead,
H.C.Watson.
|
|
|
Ref.
|
|
J Mol Biol, 1978,
118,
137-208.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Figure 1.
FIG. 1. The variation in he ean arent and heavy-atom structure amplitudes and in he
accurctcy of the hase etermination of the complete high resolution tosyl-elastse data set as a
unction of sin20/ha. (-A-A-), F,//2 -O-O--), lfHl --m--W--, --O--O---,
--A--/--) and E (-m-m--, -e-a--, -b-A-) are defined as in Tables 3 and 4.
The values or wa are iven by the right ordinate, nd those or 1Frl, lfnl and E, which are n he
same non-absolute scale, by the ordinate. A, CMBS-elastase; 0, ranyl tosyl-elastase;
H, uranyl CMBS-elastase.
|
|
Figure 10.
IG. 10. Histograms of (a) x, b) yz, (c) x3.
|
|
|
|
|
|
The above figures are
reproduced from the cited reference
with permission from Elsevier
|
|
|
Secondary reference #2
|
|
|
Title
|
|
The indirect mechanism of action of the trifluoroacetyl peptides on elastase. Enzymatic and 19f nmr studies.
|
|
|
Authors
|
|
J.L.Dimicoli,
A.Renaud,
J.Bieth.
|
|
|
Ref.
|
|
Eur J Biochem, 1980,
107,
423-432.
|
|
|
PubMed id
|
|
|
|
|
|
|
|
|
Secondary reference #3
|
|
|
Title
|
|
Crystallographic study of the binding of a trifluoroacetyl dipeptide anilide inhibitor with elastase.
|
|
|
Authors
|
|
D.L.Hughes,
L.C.Sieker,
J.Bieth,
J.L.Dimicoli.
|
|
|
Ref.
|
|
J Mol Biol, 1982,
162,
645-658.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Figure 1.
FIG. 1. Superposition f the inhibitor molecule and some neighbouring residues on the final difference
map (p,- IF,/) or TFAP in the active site region. Contours ar drawn at estimated lrvrls of 0,;5, I.0 and
1.5 I?.
|
|
Figure 3.
FIG. 3. Th active centre region in: (a) native elastase (pH 5.0); (b) tosyl-elastase; and (c) the
TFAl/elastase complex, TFAP.
|
|
|
|
|
|
The above figures are
reproduced from the cited reference
with permission from Elsevier
|
|
|
Secondary reference #4
|
|
|
Title
|
|
Structure of native porcine pancreatic elastase at 1.65 a resolutions.
|
|
|
Authors
|
|
E.Meyer,
G.Cole,
R.Radhakrishnan,
O.Epp.
|
|
|
Ref.
|
|
Acta Crystallogr B, 1988,
44,
26-38.
|
|
|
PubMed id
|
|
|
|
|
|
|
|
|
Secondary reference #5
|
|
|
Title
|
|
Structure of the product complex of acetyl-Ala-Pro-Ala with porcine pancreatic elastase at 1.65 a resolution.
|
|
|
Authors
|
|
E.F.Meyer,
R.Radhakrishnan,
G.M.Cole,
L.G.Presta.
|
|
|
Ref.
|
|
J Mol Biol, 1986,
189,
533-539.
|
|
|
PubMed id
|
|
|
|
|
|
|
|
|
|
|
|
|
